Harpagoside Inhibits RANKL-Induced Osteoclastogenesis via Syk-Btk-PLC纬2-Ca2+ Signaling Pathway and Prevents Inflammation-Mediated Bone Loss
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- 作者：Ju-Young Kim ; Sun-Hyang Park ; Jong Min Baek ; Munkhsoyol Erkhembaatar ; Min Seuk Kim ; Kwon-Ha Yoon ; Jaemin Oh ; Myeung Su Lee
- 刊名：Journal of Natural Products
- 出版年：2015
- 出版时间：September 25, 2015
- 年：2015
- 卷：78
- 期：9
- 页码：2167-2174
- 全文大小：562K
- ISSN：1520-6025
文摘
Harpagoside (HAR) is a natural compound isolated from Harpagophytum procumbens (devil鈥檚 claw) that is reported to have anti-inflammatory effects; however, these effects have not been investigated in the context of bone development. The current study describes for the first time that HAR inhibits receptor activator of nuclear factor 魏B ligand (RANKL)-induced osteoclastogenesis in vitro and suppresses inflammation-induced bone loss in a mouse model. HAR also inhibited the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose-dependent manner as well as the activity of mature osteoclasts, including filamentous actin (F-actin) ring formation and bone matrix breakdown. This involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of Syk-Btk-PLC纬2-Ca2+ in RANKL-dependent early signaling, as well as the activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which resulted in the down-regulation of various target genes. Consistent with these in vitro results, HAR blocked lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model. However, HAR did not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model. These results suggest that HAR is a valuable agent against inflammation-related bone disorders but not osteoporosis induced by hormonal abnormalities.